Paroxysmal nocturnal hemoglobinuria (PNH) is a blood disorder that affects the red blood cells. The problem begins in the bone marrow, where blood cells are made. In PNH, red blood cells break apart too early because they do not have the proteins they need to stay protected. This can lead to anemia (low red blood cells), dark urine (pee), and a higher risk of blood clots.
PNH is rare in children and teens and is more common in adults. It is a long-term condition. Patients require close monitoring.
Treatment for PNH may include:
Medicines that protect red blood cells and lower the risk of blood clots
Supportive care (blood transfusions)
Stem cell transplant (bone marrow transplant) for children with severe disease or bone marrow failure
The name paroxysmal nocturnal hemoglobinuria can be confusing. It comes from early ideas about the disease:
Paroxysmal means sudden.
Nocturnal means night. Doctors once thought red blood cells broke apart mostly at night because dark urine was often seen in the morning. Doctors now know this can happen during any time of day.
Hemoglobinuria means hemoglobin (from broken red blood cells) shows up in the urine.
Symptoms of paroxysmal nocturnal hemoglobinuria
Signs and symptoms of PNH can be mild to severe. Some children may have no symptoms at first.
Low red blood cells, also called anemia, are a common problem in PNH. Signs and symptoms of anemia may include:
When red blood cells break apart, other symptoms may occur, including:
Dark-colored urine (pee)
Pain in the abdomen (belly), chest, or back
Trouble swallowing
Kidney or liver problems
Call your child’s health care provider right away or seek emergency care if your child has symptoms of blood clots:
Sudden swelling, pain, warmth or redness in an arm or leg
Chest pain or trouble breathing
Severe headache
Symptoms of PNH can change over time. New symptoms may appear as the disease progresses.
Risk factors for paroxysmal nocturnal hemoglobinuria
Many patients with PNH have no known risk factors. PNH is not inherited or passed down in families. It is more common in adults than in children.
Children with acquired aplastic anemia, have a higher risk of developing PNH.
Causes of paroxysmal nocturnal hemoglobinuria
PNH is caused by a gene change (mutation) in a gene called PIGA. This change happens in bone marrow. It is an acquired change, meaning it develops during a person’s life and is not inherited from parents. The gene mutation occurs randomly by chance.
A healthy PIGA gene helps blood cells make important protective proteins. When this gene is changed, the body cannot make these proteins. Without them, the immune system can attack and destroy red blood cells. This leads to PNH symptoms.
Diagnosis of paroxysmal nocturnal hemoglobinuria
Your child’s health care provider will do a physical exam and ask about medical history. They will order several tests to check how the blood and bone marrow are working.
Tests to diagnose PNH may include:
Flow cytometry: This is the main test for PNH. It checks blood cells for missing protective surface proteins. Cells that lack these proteins are a key sign of PNH.
Complete blood count: This test measures the number of red blood cells, white blood cells, and platelets. A low red blood cell count can be a sign of PNH.
Other blood tests: Other blood tests help show whether red blood cells are being destroyed too early. They may include:
LDH (lactate dehydrogenase): High levels can be a sign of red blood cell damage.
Haptoglobin: Low levels are a sign that red blood cells are being destroyed too early.
Reticulocyte count: This test measures the number of young red blood cells in your child’s body. A high reticulocyte count means the bone marrow has to make more cells to replace damaged ones.
Bilirubin test: Bilirubin is made by the liver when red blood cells are broken down. High levels may be seen in PNH.
Direct antiglobulin test (Coombs test): This test can help rule out other causes. It shows if the body is making antibodies against red blood cells.
Urine tests: A urinalysis may be done to check for hemoglobin or blood in the urine.
Bone marrow aspiration and biopsy: This test helps show how well blood cells are being made and can identify acquired genetic changes and other bone marrow disorders.
Genetic counseling may be offered, especially in patients who previously had aplastic anemia.
Treatment of paroxysmal nocturnal hemoglobinuria
Treatment depends on your child’s symptoms and how severe the disease is. Some children only need close monitoring. Others need treatments such as:
Medicines
Targeted medicines called complement inhibitors help protect red blood cells from being destroyed too early. Examples include eculizumab, ravulizumab, and iptacopan. These medicines can reduce anemia, lower the risk of blood clots, and improve energy levels. Because these medicines affect the immune system, children taking them must get certain vaccines to help prevent serious infections.
A stem cell transplant is the only known cure for PNH. It replaces damaged bone marrow with healthy cells from a donor. Because transplants have serious risks, they are usually recommended only for children with severe disease or bone marrow failure which can present with drop in other blood counts (neutrophils and platelets).
Prognosis for paroxysmal nocturnal hemoglobinuria
With treatment, many children live full, active lives.
Your child’s outlook depends on:
How severe their disease is
How well they respond to treatment
Whether they have other bone marrow problems
Ask your child’s care team about their specific case.
Living with paroxysmal nocturnal hemoglobinuria
If your child has PNH, there are steps you can take to help manage the disease and prevent complications. Work closely with your care team to develop a care plan that is right for your child.
Here are some ways to help manage PNH:
Keep all medical appointments: Regular blood tests and checkups are important. Contact your child’s care team if symptoms change.
Take steps to prevent infection: Help your child wash their hands often, keep living spaces clean, and avoid people who are sick. Make sure your child stays up to date on vaccines and takes any prescribed medicines as instructed.
Tell others about your child’s condition: Make sure that dentists, doctors, emergency teams, and other health care providers know your child has PNH and what medicines they take.
Talk to your child’s care provider before starting new medicines or supplements: Some medicines can affect blood cells or interact with PNH treatments. Your care provider can help you choose what medicines and supplements are safe for your child.
Manage activities: Help your child pace themselves. When hemoglobin is low, avoid physical activities that are too hard for their body. Encourage them to stop and rest when they need to.
Living with a PNH can be stressful. Support may include patient support groups, counseling to support mental health, and help from social workers or child life specialists. These resources can help your child and family manage emotional and practical challenges.
When to call your care team
Contact your care team if your child has:
New or worsening fatigue or weakness
Dark-colored urine
Increase in fatigue or weakness
Sudden or severe headache, belly pain, or back pain
Shortness of breath, fast heartbeat, or chest pain
Swelling, pain, warmth, or redness in an arm or leg (signs of a blood clot)
Talk to your care team about any questions or concerns you may have and be sure you know what to do in an emergency.
Questions to ask your care team
How severe is my child’s PNH?
What tests does my child need to monitor their condition?
What treatments are available for PNH and what options are best for my child?
What are the risks or complications of PNH?
Are there any activities my child needs to limit or avoid?
Are there any diet or lifestyle changes that can help manage PNH?
How can we lower the risk of blood clots?
How often does my child need follow-up visits?
What symptoms should we report right away?
Should we consider a clinical trial for PNH?
Key points about paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is a blood disorder caused by a change in the PIGA gene in bone marrow cells.
PNH causes early red blood cell breakdown, which can lead to anemia, dark-colored urine, and a higher risk of blood clots.
Treatments for PNH include medicines to protect red blood cells, red blood cell transfusions, and care to help manage symptoms and prevent complications.
A stem cell transplant is the only cure for PNH, but it is used only in select cases.
With proper care, many children with PNH live long and healthy lives.
Diagnosing a blood disorder usually involves several steps including a physical exam, health history, and lab tests. Learn how blood disorders are diagnosed.
A stem cell transplant (bone marrow transplant) may be used as a treatment for some childhood cancers and blood disorders. Learn more about stem cell transplants.
